Sensor array mounted on flexible carrier

ABSTRACT

A sensor apparatus is disclosed herein. The sensor apparatus includes a flexible carrier that is elongated along a length of the carrier. The sensor apparatus also includes a plurality of analysis zones carried by the carrier. The analysis zones are spaced-apart from one another along the length of the carrier. The sensor apparatus further includes first and second spaced-apart electrodes carried by the flexible carrier. The first and second electrodes have lengths that extend along the length of the carrier. At least one of the first and second electrodes includes analyte sensing chemistry. The first and second electrodes extending across and contact the plurality of analysis zones.

This application is being filed on 5 Jan. 2012, as a PCT InternationalPatent application in the name of Pepex Biomedical, Inc., a U.S.national corporation, applicant for the designation of all countriesexcept the US, and James L. Say, a citizen of the U.S., applicant forthe designation of the US only, and claims priority to U.S. ProvisionalApplication Ser. No. 61/430,393 filed Jan. 6, 2011, the subject matterof which is incorporated by reference in its entirety.

TECHNICAL FIELD

The present disclosure relates generally to sensors. More particularly,the present disclosure relates to sensors for measuring bio-analyteconcentrations in blood samples.

BACKGROUND

Electrochemical bio-sensors have been developed for sensing (e.g.,detecting or measuring) bio-analyte concentrations in fluid samples. Forexample, U.S. Pat. Nos. 5,264,105; 5,356,786; 5,262,035; 5,320,725; and6,464,849, which are hereby incorporated by reference in theirentireties, disclose wired enzyme sensors for sensing analytes, such aslactate or glucose. Wired enzyme sensors have been widely used in bloodglucose monitoring systems adapted for home use by diabetics to allowblood glucose levels to be closely monitored. Other example types ofblood glucose monitoring systems are disclosed by U.S. Pat. Nos.5,575,403; 6,379,317; and 6,893,545.

SUMMARY

One aspect of the present disclosure relates to a wired enzyme sensorsystem that allows for low cost manufacturing and facilitatesminiaturization.

Another aspect of the present disclosure relates to a wired enzymesensor system conducive for continuous automated manufacturing usingfiber sensor technology.

A further aspect of the present disclosure relates to a sensor systemthat allows for enhanced manufacturing control to provide betteraccuracy and repeatability.

Still another aspect of the present disclosure relates to a sensorsystem including a plurality of sample fluid analysis zones carried onan elongated, flexible dielectric carrier (e.g., a tape, sheet, film,web, layer, substrate, media etc.). The analysis zones are spaced-apartfrom one another along a length of the carrier and are separated fromeach other by gaps. Capillary flow promoting structures can be providedat each of the analysis zones for encouraging a sample fluid (e.g.,blood) to flow into the analysis zone by capillary action. Two elongatedelectrodes extend along the length of the carrier. The electrodes eachtraverse the gaps between the analysis zones and contact each of theanalysis zones. One of the electrodes can include a working electrodeand the other of the electrodes can include a reference electrode or acounter/reference electrode. To test a fluid sample for an analyteconcentration, one of the analysis zones is wetted with the fluid sampleand the electrodes contacting the analysis zone are used to generate areading indicative of the analyte concentration. After the analyteconcentration has been determined and another sample is desired to beanalyzed, the electrodes are severed at a location between the usedanalysis zone and the unused analysis zone(s) to electrically isolatethe used analysis zone from the portions of the electrodes contactingthe unused analysis zone(s). Thereafter, a reading can be taken at thenext unused analysis zone. This process can be repeated until all of theanalysis zones carried by the carrier have been used to test fluidsamples.

A variety of additional aspects will be set forth within the descriptionthat follows. The aspects can relate to individual features and tocombinations of features. It is to be understood that both the foregoinggeneral description and the following detailed description are exemplaryand explanatory only and are not restrictive of the broad concepts uponwhich the embodiments disclosed herein are based.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a sensor array and flexible carrier inaccordance with the principles of the present disclosure;

FIG. 2 is a plan view of the sensor array and flexible carrier of FIG.1;

FIG. 3 is a side view of the sensor array and flexible carrier of FIG.1;

FIG. 4 shows a portion of a flexible carrier of FIG. 1 with othercomponents removed;

FIG. 5 shows the sensor array and flexible carrier of FIG. 1incorporated into an analyte monitoring unit/system, the sensor array isbeing used to analyze a first blood sample at a first analysis zone;

FIG. 6 shows the sensor array being used to analyze a second bloodsample at a second analysis zone;

FIG. 7 shows the sensor array being used to analyze a third blood sampleat a third analysis zone;

FIG. 8 shows the sensor array being used to analyze a fourth bloodsample at a fourth analysis zone;

FIG. 9 shows an analyte monitoring unit adapted for use with the sensorarray and flexible carrier of FIG. 1;

FIG. 10 shows a drive gear of the analyte monitoring unit of FIG. 9; and

FIG. 11 shows a portion of the analyte monitoring unit of FIG. 9 afterthe drive gear has been removed.

DETAILED DESCRIPTION

Reference will now be made in detail to exemplary aspects of the presentdisclosure which are illustrated in the accompanying drawings. Whereverpossible, the same reference numbers will be used throughout thedrawings to refer to the same or like parts.

The following definitions are provided for terms used herein:

A “working electrode” is an electrode at which the analyte (or a secondcompound whose level depends on the level of the analyte) iselectrooxidized or electroreduced with or without the agency of anelectron transfer agent.

A “reference electrode” is an electrode used in measuring the potentialof the working electrode. The reference electrode should have agenerally constant electrochemical potential as long as no current flowsthrough it. As used herein, the term “reference electrode” includespseudo-reference electrodes. In the context of the disclosure, the term“reference electrode” can include reference electrodes which alsofunction as counter electrodes (i.e., a counter/reference electrode).

A “counter electrode” refers to an electrode paired with a workingelectrode to form an electrochemical cell. In use, electrical currentpasses through the working and counter electrodes. The electricalcurrent passing through the counter electrode is equal in magnitude andopposite in sign to the current passing through the working electrode.In the context of the disclosure, the term “counter electrode” caninclude counter electrodes which also function as reference electrodes(i.e., a counter/reference electrode).

A “counter/reference electrode” is an electrode that functions as both acounter electrode and a reference electrode.

An “electrochemical sensing system” is a system configured to detect thepresence and/or measure the level of an analyte in a sample viaelectrochemical oxidation and reduction reactions on the sensor. Thesereactions are converted (e.g., transduced) to an electrical signal thatcan be correlated to an amount, concentration, or level of an analyte inthe sample. Further details about electrochemical sensing systems,working electrodes, counter electrodes and reference electrodes can befound at U.S. Pat. No. 6,560,471, the disclosure of which is herebyincorporated herein by reference in its entirety.

“Electrolysis” is the electrooxidation or electroreduction of a compoundeither directly at an electrode or via one or more electron transferagents.

An “electron transfer agent” is a compound that carries electronsbetween the analyte and the working electrode either directly or incooperation with other electron transfer agents. One example of anelectron transfer agent is a redox mediator.

A “sensing layer” is a component of the sensor which includesconstituents that facilitate the electrolysis of the analyte. Thesensing layer may include constituents such as an electron transferagent, a catalyst which catalyzes a reaction of the analyte to produce aresponse at the electrode, or both.

FIGS. 1-4 illustrate a sensor array 20 in accordance with the principlesof the present disclosure. The sensor array 20 includes a plurality ofsample fluid analysis zones 22 a-22 d carried on an elongated, flexibledielectric carrier 24 (e.g., a tape, sheet, film, web, layer, substrate,media etc.). The analysis zones are spaced-apart from one another alonga length L of the carrier 24 and are separated from each other by gaps26 a-26 c. Two elongated electrodes 28, 30 extend along the length L ofthe carrier 24. The electrodes 28, 30 each traverse the gaps between theanalysis zones and contact each of the analysis zones. One of theelectrodes 28, 30 can include a working electrode and the other of theelectrodes 28, 30 can include a reference electrode or acounter/reference electrode.

While, for illustration purposes, only four fluid analysis zones areshown at FIG. 1, it will be appreciated that in preferred embodimentsmany more than four analysis zones will be provided on each carrier. Forexample, in certain embodiments, at least 25, or at least 50, or atleast 75, or at least 100 analysis zones can be provided on eachcarrier.

Capillary flow promoting structures can be provided at each of theanalysis zones for encouraging a sample fluid (blood) to flowinto/across the analysis zone by capillary action. Capillary flow can bein a direction that extends across a width W of the carrier 24. As shownat FIGS. 1-3, capillary flow promoting structures 32 can be providedwithin wells 36 defined by the carrier 24 at each analysis zone. Thecapillary flow promoting structures 32 can include cast-in-place foam(e.g., open cell foam), ribbon filter media, capillary yearn or othercapillary flow inducing material. The capillary flow promotingstructures 32 can also include surface texturing provided on the carrier24. The capillary flow promoting structures 32 can also includehematocrit filters. Indentations 40 can be provided in the side of thecarrier 24 at each of the analysis zones to provide a capillary flowdirector profile. Prior to use, the analysis zones are preferably dryand not electrically conductive.

The carrier 24 includes structures for mounting the electrodes 28, 30 tothe top side of the carrier 24. As shown at FIG. 4, such structures caninclude grooves 50 in which the electrodes 28, 30 are affixed (e.g.,adhesively affixed).

As described later in the description, during use of the sensor array 20it is desirable to sever (i.e., break, disrupt, interrupt, cut) theelectrodes 28, 30 at the gaps. The electrodes can be mechanicallysevered or severed using other means such as a laser. A preferred methodfor severing the electrodes at the gaps is to use a punching process. Toaccommodate a punching process, punch holes 60 are provided at each ofthe gaps. The electrodes 28, 30 traverse the punch holes 60.

The carrier 24 is preferably made of a dielectric material and ispreferably relatively flexible. In one embodiment, the carrier 24 can bewrapped in a cylinder having a diameter less than or equal to 3 incheswithout breaking. In another embodiment, the carrier 24 can be wrappedin a cylinder having a diameter less than or equal to 2 inches withoutbreaking.

In one embodiment, the electrode 28 is in contact with a sensing layerand functions as a working electrode and the electrode 30 can functionas a reference/counter electrode. In other embodiments, separateworking, reference and counter electrodes can be provided in fluidcommunication with the analysis zones. The electrodes 28, 30 arepreferably threads, fibers, wires, or other elongated members.

In one embodiment, the working electrode can include an elongated memberthat is coated or otherwise covered with a sensing layer and thereference/counter electrode can include any elongated member, such as awire or fiber that is coated or otherwise covered with a layer, such assilver chloride. Preferably, at least a portion of each elongated memberis electrically conductive. In certain embodiments, each elongatedmember can include a metal wire or a glassy carbon fiber. In still otherembodiments, each elongated member can each have a composite structureand can include a fiber having a dielectric core surrounded by aconductive layer suitable for forming an electrode.

A preferred composite fiber is sold under the name Resistat® byShakespeare Conductive Fibers LLC. This composite fiber includes acomposite nylon, monofilament, conductive thread material madeconductive by the suffusion of about a 1 micron layer of carbonizednylon isomer onto a dielectric nylon core material. The Resistat®material is comprised of isomers of nylon to create the basic two layercomposite thread. However, many other polymers are available for theconstruction, such as: polyethylene terephthalate, nylon 6, nylon 6,6,cellulose, polypropylene cellulose acetate, polyacrylonitrile andcopolymers of polyacrylonitrile for a first component and polymers suchas of polyethylene terephthalate, nylon 6, nylon 6,6, cellulose,polypropylene cellulose acetate, polyacrylonitrile and copolymers ofpolyacrylonitrile as constituents of a second component. Inherentlyconductive polymers (ICP) such as doped polyanaline or polypyrolle canbe incorporated into the conductive layer along with the carbon tocomplete the formulation. In certain embodiments, the ICP can be used asthe electrode surface alone or in conjunction with carbon. The Resistat®fiber is availability in diameters of 0.0025 to 0.016 inches, which issuitable for sensor electrodes configured in accordance with theprinciples of the present disclosure. Example patents disclosingcomposite fibers suitable for use in practicing sensor modulesconfigured in accordance with the principles of the present disclosureinclude U.S. Pat. Nos. 3,823,035; 4,255,487; 4,545,835 and 4,704,311,which are hereby incorporated herein by reference in their entireties.

The sensing layers provided at working electrodes of sensor modulesconfigured in accordance with the principles of the present disclosurecan include a sensing chemistry, such as a redox compound or mediator.The term redox compound is used herein to mean a compound that can beoxidized or reduced. Example redox compounds include transition metalcomplexes with organic ligands. Preferred redox compounds/mediatorsinclude osmium transition metal complexes with one or more ligandshaving a nitrogen containing heterocycle such as 2,2′-bipyridine. Thesensing material also can include a redox enzyme. A redox enzyme is anenzyme that catalyzes an oxidation or reduction of an analyte. Forexample, a glucose oxidase or glucose dehydrogenase can be used when theanalyte is glucose. Also, a lactate oxidase or lactate dehydrogenasefills this role when the analyte is lactate. In sensor systems, such asthe one being described, these enzymes catalyze the electrolysis of ananalyte by transferring electrons between the analyte and the electrodevia the redox compound. Further information regarding sensing chemistrycan be found at U.S. Pat. Nos. 5,264,105; 5,356,786; 5,262,035; and5,320,725, which were previously incorporated by reference in theirentireties.

During sample analysis (e.g., blood analysis) at one of the analysiszones, a voltage can be applied through the analysis zone between theelectrodes 28, 30. When the potential is applied, an electrical currentwill flow through the fluid sample between the electrodes 28, 30. Thecurrent is a result of the oxidation or reduction of an analyte, such asglucose, in the volume of fluid sample located within the analysis zone.This electrochemical reaction occurs via the electron transfer agent inthe sensing layer and an optional electron transfer catalyst/enzyme inthe sensing layer. By measuring the current flow generated at a givenpotential (e.g., with a controller described herein), the concentrationof a given analyte (e.g., glucose) in the fluid sample can bedetermined. Those skilled in the art will recognize that currentmeasurements can be obtained by a variety of techniques including, amongother things, coulometric, potentiometric, perometric, voltometric, andother electrochemical techniques.

Referring to FIG. 5, the sensor array 20 and carrier 24 are shownincorporated as a sub-component of an analyte monitoring unit 120. Theunit 120 includes a holder that houses a controller 122. The housing canalso include a holder that holds the sensor array 20 and carrier 24. Thehousing can further include a drive arrangement for moving the carrier24 to consecutively index the analysis zones to a use position 80defined by the unit 120.

In general, the unit 120 includes the controller 121, an actuator 123,and input lines 125, 127 extending from contacts 128, 130. Thecontroller 122 controls the actuator arrangement 123 for disposabledriving skin piercing members 90 (e.g., needles, lancets, canulas orlike structures) between the retracted and extended positions to obtaina fluid sample (e.g., a blood sample) at the use position 80. Thecontroller 121 can include a microcontroller, a mechanical controller,software driven controller, a hardware driven controller, a firmwaredriven controller, etc. The controller can include a microprocessor thatinterfaces with memory.

The input lines 125, 127 carry data/signals/readings (e.g., voltagevalues) generated between the electrodes 28, 30 at a given one of theanalysis zone being used during analysis of a fluid sample to thecontroller 121 for analysis. The controller 121 converts thedata/signals/reading to an analyte concentration level (e.g., a bloodglucose reading) or other desired information. The controller 121 causesa display 131 to indicate the processed information to the user. Otherinformation also can be presented on the display 131. In one embodiment,the display 131 is a visual display. In other embodiments, an audiodisplay also can be used. Additional information can be provided to theprocessor 121 via a user interface 129 (e.g., buttons, switches, etc.).

In use of the unit 120, the carrier 24 is indexed to align the analysiszone 22 a with the use position 80 of the unit 120 (see FIG. 5). A skinpiercing member 90 is then loaded into the unit at the use position 80and the person places their finger at the indentation 40 correspondingto the analysis zone 22 a. The actuator 123 then extends the skinpiecing member 90 causing a sample site at the finger in the form of apuncture wound. Blood from the sample site wets the analysis zone 22 aand flows by capillary action across the analysis zone 22 a. Thecontacts 128, 130 are placed in electrical contact with the electrodes28, 30 at the gap 26 a. The controller 121, via the lines 125, 127 andcontacts 128, 130, then causes a voltage to be applied between theelectrodes 28, 30 and across the wetted analysis zone 22 a. Thecontroller 121 then takes a reading and determines an analyte (e.g.,glucose) concentration in the blood sample. Once the reading has beentaken, the skin piercing member 90 can be disposed of and the carrier isindexed such that the analysis zone 22 b and the gap 26 b are positionedat the use position 80 (see FIG. 6). In the use position 80, thecontacts 128, 130 engage the electrodes 28, 30 at the gap 26 b. Also,the controller 121 can actuate a punch which severs the electrodes 28,30 at the gap 26 a such that the used/wetted analysis zone 22 a iselectrically isolated from the portions of the electrodes 28, 30traversing the unused analysis zones 22 b-22 d.

To analyze a second blood sample, a new skin piercing member 90 isloaded into the unit and the process is repeated causing the analysiszone 22 b to be wetted with the second blood sample. A voltage is thenapplied between the electrodes 28, 30 and across the analysis zone 22 band a reading is taken. Once the reading has been taken, the skinpiercing member 90 can be disposed of and the carrier is indexed suchthat the analysis zone 22 c and the gap 26 c are positioned at the useposition 80 (see FIG. 7). In the use position, the contacts 128, 130engage the electrodes 28, 30 at the gap 26 c. Also, the controller 121can actuate a punch which severs the electrodes 28, 30 at the gap 26 bsuch that the used/wetted analysis zone 22 b is electrically isolatedfrom the portions of the electrodes 28, 30 traversing the unusedanalysis zones 22 c-22 d.

To analyze a third blood sample, a new skin piercing member 90 is loadedinto the unit and the process is repeated causing the analysis zone 22 cto be wetted with the third blood sample. A voltage is then appliedbetween the electrodes 28, 30 and across the analysis zone 22 c and areading is taken. Once the reading has been taken, the skin piercingmember 90 can be disposed of and the carrier is indexed such that theanalysis zone 22 d and the gap 26 d are positioned at the use position80 (see FIG. 8). In the use position, the contacts 128, 130 engage theelectrodes 28, 30 at the gap 26 d. Also, the controller 121 can actuatea punch which severs the electrodes 28, 30 at the gap 26 c such that theused/wetted analysis zone 22 c is electrically isolated from theportions of the electrodes 28, 30 traversing the unused analysis zones22 d. Analysis zone is then ready for use as described above. Moreover,it will be appreciated that the process can be consecutively repeateduntil all of the analysis zones on the carrier have been used.Thereafter, the carrier 24 can be disposed of and replaced with a likecarrier having unused analysis zones.

FIGS. 9-11 show a hand-held analyte monitoring unit 200 that can be usedwith the sensor array 20 and carrier 24 of FIG. 1. The unit 200 includesa main housing 202 in which a controller can be housed. The main housing202 can also include an indexing drive. A display and a user interfacecan be provided on the back side of the main housing 202. The mainhousing 202 includes a use location 80 (i.e., a sampling location)defining a rear receptacle 204 for mounting a skin piercing memberactuator. The skin piercing member actuator is adapted to extend a skinpiercing member through an opening 206 at the use location 80. The unit200 also includes a drive gear 210 that mounts on the main housing 202and is rotated by the indexing drive to index the carrier 24 toconsecutively move unused analysis zones to the use location 80. Thedrive gear 210 includes an inner cylindrical surface 212. The carrier 24is rolled/wrapped in a cylinder and secured to the cylindrical surface212. The drive gear/drive ring can be disposable and the carrier can bepre-attached to the drive gear at the manufacturing facility orelsewhere before purchase by a consumer.

In alternative embodiments, only one of the electrodes 28, 30 may besevered to isolate used/spent analysis zones from unused analysis zones.By severing at least one of the electrodes 28, 30 at a gap between theused/spent analysis zone and the unused analysis zones, avoltage/potential is prevented from being applied across the used/spentanalysis zone when a subsequent analysis zone is being used to analyze afluid sample.

1. A sensor apparatus comprising: a flexible carrier that is elongatedalong a length of the carrier; a plurality of analysis zones carried bythe carrier, the analysis zones being spaced-apart from one anotheralong the length of the carrier; and first and second spaced-apartelectrodes carried by the flexible carrier, the first and secondelectrodes having lengths that extend along the length of the carrier,at least one of the first and second electrodes including analytesensing chemistry, the first and second electrodes extending across andcontacting the plurality of analysis zones.
 2. The sensor apparatus ofclaim 1, wherein the plurality of analysis zones are formed by recessesin the flexible carrier, the recesses being positioned below the firstand second electrodes.
 3. The sensor apparatus of claim 2, wherein therecesses extend across a width of the carrier.
 4. The sensor apparatusof claim 3, wherein the plurality of analysis zones include capillaryflow enhancing structures positioned within the recesses for encouragingcapillary flow across the width of the carrier.
 5. The sensor apparatusof claim 4, further comprising punch holes defined through the carrierat a location between the analysis zones, wherein the electrodes extendacross the punch holes.
 6. The sensor apparatus of claim 4, wherein thecarrier includes a side surface defining indentations at each of theanalysis zones.
 7. The sensor apparatus of claim 1, wherein the carrierdefines grooves in which the first and second electrodes are mounted. 8.A method for using the sensor apparatus of claim 1, the methodcomprising: wetting a first analysis zone of the plurality of analysiszones with a first volume of sample fluid; taking a first reading at thefirst analysis zone by applying a first voltage across the wetted firstanalysis zone and between the first and second electrodes; wetting asecond analysis zone of the plurality of analysis zones with a secondvolume of the sample fluid; taking a second reading at the secondanalysis zone by applying a second voltage across the wetted secondanalysis zone and between the first and second electrodes; preventing avoltage from being applied across the first wetted analysis zone whenthe second reading is being taken at the wetted second analysis zone bysevering at least one of the first and second electrodes at a locationbetween the wetted first analysis zone and the wetted second analysiszone.
 9. The method of claim 8, wherein the analysis zones arenon-conductive until the analysis zones are wetted.